Pre-filled package containing unit dose of medical gas and method of making same

ABSTRACT

A unit dose, gas-filled syringe is provided which is filled with gas and packaged in a gas barrier material prior to use to increase shelf-life, that is, to minimize gas leakage and dilution of the contents of the syringe. The syringe is filled with a selected gas and sealed inside a container made from a high gas barrier material. The container is also filled with the selected gas. The container material is selected to have a gas transmission rate sufficient to prevent the selected gas from diffusing out of the container into the atmosphere. The volume of gas in the container is greater that atmospheric pressure to prevent atmospheric contaminants from entering the container and syringe.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application is a continuation-in-part application of Ser.No. 08/838,824, filed Apr. 10, 1997, which is hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

[0002] The invention relates generally to a pre-filled packagecontaining a unit dose of medical gas and a method of making same. Theinvention is further directed to a method of introducing a unit dose fora gas into a patient using the prefilled syringe.

BACKGROUND OF THE INVENTION

[0003] Gas-filled syringes are useful for a number of applications suchas surgical procedures involving the injection of a gas bubble into apatient's body. For example, a retinal tear can be treated using anintraocular surgical procedure during which a gas such as sulfurhexafluoride (SF₆) or perfluoropropane (C₃F₈) is injected into the eyefor gas tamponage. Carbon dioxide (CO₂) gas can be injected into a bloodvessel to facilitate percutaneous angioscopy. Nitric oxide (NO) gas andNO-releasing compounds can also be used to treat a number of medicalconditions. For example, NO and NO-releasing compounds can be used fortreatment of male impotence, inhibition of DNA synthesis andmitochondrial respiration in tumor cells, and relaxation of vascularsmooth muscle for control of hypertension.

[0004] Gases used for surgery are often expensive and not available forpurchase in ready-to-use form. Currently, gases for surgical proceduresare purchased in a pressurized tank. Syringes are filled directly fromthe tank using a filling line. When a syringe is disconnected from thefilling line, the gas in the filling line is released into theatmosphere. Thus, this method of preparing syringes for surgery isdisadvantageous because a significant amount of gas is wasted. Due tothe busy environment of a hospital, shut-off valves on gas tanks arefrequently left open accidentally, causing an even greater amount of gasto be wasted than when gas syringes are being filled.

[0005] In addition to the problem of wasting expensive gases, a moreserious clinical problem associated with filling syringes from gas tanksis dilution of the gas in the syringe prior to surgery. Syringes aresometimes prepared on the morning of the day they are to be used insurgery. The syringes are then placed in the operating room with othersurgical devices until they are needed, which can be several hourslater. Experiments have shown that leakage of gas from a syringe over arelatively short period of time can cause clinically significantdilution of the gas dose and therefore increase the risk of surgicalcomplications. For instance, the concentration of sulfur hexafluoride ina plastic syringe has been observed to decrease from 97% at 30 secondsafter aspiration to 76% at 60 minutes and 2% at 18 hours pastaspiration.

SUMMARY OF THE INVENTION

[0006] The present invention overcomes the above-described disadvantagesassociated with known methods for preparing gas-filled syringes, whilealso realizing a number of advantages. In accordance with one aspect ofthe invention, a unit dose, gas-filled syringe is provided which isfilled with gas and packaged in a gas barrier material prior to use toincrease shelf-life, that is, minimize gas leakage and dilution of thecontents of the syringe. The syringe is initially filled with a selectedgas and sealed inside a container made from a high gas barrier material.The container is then also filled with the selected gas. The containermaterial is selected to have a gas transmission rate sufficient toprevent the selected gas from diffusing out of the container into theatmosphere and to prevent atmospheric gas contaminants from entering thecontainer. The gas is a pharmaceutically acceptable gas for injectinginto the body of an animal. The gas is substantially free of oxygen andair and is at least 70% pure, and preferably 97% pure by volume.

[0007] In accordance with another aspect of the present invention, amethod of packaging a gas-filled syringe is provided which comprises thesteps of forming a container from a gas barrier material to enclose thesyringe, placing the gas-filled syringe in the container, filling thecontainer with the same gas as in the pre-filled gas syringe, andsealing the container to retain the gas and the syringe therein.

[0008] In accordance with yet another aspect of the present invention, amethod of packaging a gas-filled syringe is provided which comprises thesteps of forming a container from a gas barrier material to enclose thesyringe, the container comprising a valve, placing the gas-filledsyringe in the container, sealing the container to retain the syringetherein, evacuating the sealed container, and filling the container withthe same gas as in the syringe using the valve.

[0009] In accordance with still yet another aspect of the presentinvention, a method of preparing a gas-filled syringe is provided whichcomprises the step of filling a container with a predetermined volume ofa selected gas via an opening therein. The container is formed from ahigh gas barrier material to prevent gas from escaping from thecontainer once the opening is sealed. The method further comprises thestep of puncturing the container with the syringe needle and drawing thegas into the syringe by retracting the syringe plunger.

[0010] A further aspect of the invention is basically attained byproviding a method of introducing a gas into the eye during eye surgery,the method comprising the steps of providing a clean and sterileprefilled syringe containing a unit dose of a pharmaceuticallyacceptable gas and being substantially free of air and oxygen, thesyringe having a syringe barrel, a gas delivery outlet, and a plunger.The syringe is completely enclosed in a substantially gas impermeablecontainer, and the container has an internal volume surrounding thesyringe filled with the pharmaceutically acceptable gas at a pressure atleast substantially equal to atmospheric pressure. The syringe isremoved from the container, and the gas delivery outlet is introducedinto the eye of a patient and the gas is introduced into the eye.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] These and other features and advantages of the present inventionwill be more readily apprehended from the following detailed descriptionwhen read in connection with the appended drawings, in which:

[0012]FIG. 1 is an isometric view of a container and cover constructedin accordance with an embodiment of the present invention for containinga gas and enclosing a syringe filled with gas;

[0013]FIG. 2 is a side cross-sectional view of the container and coverdepicted in FIG. 1 showing the syringe contained therein;

[0014]FIG. 3 is a top view of the container depicted in FIG. 1 withoutthe cover or syringe;

[0015]FIG. 4 is an isometric view of a container constructed inaccordance with an embodiment of the present invention for containing agas and enclosing a syringe filled with gas;

[0016]FIG. 5 is a side cross-sectional view of the container depicted inFIG. 4 showing the syringe contained therein;

[0017]FIG. 6 is a side cross-sectional view of a container constructedin accordance with another embodiment of the present invention forcontaining a gas; and

[0018]FIG. 7 is a top view of a syringe and canister in a container in afurther embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] With reference to FIG. 1, a container 10 for enclosing a gassyringe 12 is shown in accordance with an embodiment of the presentinvention. Before describing the container 10, an exemplary syringe 12,as shown in FIG. 2, will be described. It is to be understood that othertypes of gas-filled syringes can be used in accordance with the presentinvention. The exemplary gas syringe 12 comprises a tubular housing 14defining a syringe barrel having longitudinally cylindrical section 16,a frustoconical section 18 and a gas delivery outlet forming a gasdispensing tip 20 which are all preferably formed as an integral,unitary member. The tubular housing can be formed from a material with ahigh degree of gas impermeability such as glass. The tubular housing,however, can be a gas permeable material such as plastic since thecontainer 10 of the present invention is designed to prevent dilutionand contamination of the syringe contents, as will be described infurther detail below.

[0020] With continued reference to FIG. 2, the interior circumference ofthe tubular housing 14 defines a cavity 22 which can be filled with aselected gas in a conventional manner. The gas is retained within thecavity 22 by a plunger 24. The end of the plunger 24 that is proximalwith respect to the frustoconical section 18 of the housing 14 can beprovided with a stopper 28 which is dimensioned to slidably engage theinner circumference of the cylindrical section 16 of the tubular housing14 to controllably change the level of gas pressurization within thecavity 22. The tip 20 can be fitted with a removable cap 30. Thesyringe, however, can be open at the tip 20, or have a cannula or needleor other delivery device on the tip 20, or have an integral needle ortube molded on the front of the syringe. In any case, the container 10is designed to prevent the gas in the syringe 12 from being diluted orcontaminated by atmospheric air or contaminants regardless of whetherthe cavity 22 is completely sealed.

[0021] With reference to FIGS. 1, 2 and 3, the container 10 comprises abottom portion 32 and a top portion 44. In accordance with an embodimentof the present invention, the bottom portion 32 is preferably molded orotherwise formed to create a trough or open container dimensioned to atleast accommodate the syringe 10 having its plunger 24 at leastpartially withdrawn from the cavity 22 of the housing 14. For example,the bottom portion 32 can comprise a bottom wall 38 and four side walls34, 36, 38 and 40 which preferably form a unitary, integral memberdefining a cavity 46 in which the syringe is placed. The tops of theside walls 34, 36, 38 and 40 are each provided with a flange 48, 50, 52and 54. The top portion 44 is dimensioned to cover the opening 56 of thebottom portion 32 of the container 10, as well as engage each flange 48,50, 52 and 54. The top portion 44 and the bottom portion therefore canbe sealed together using, for example, an adhesive 51 on the flanges 48,50, 52 and 54. Alternatively, the material from which the top portion 44and the bottom portion 32 are formed can be fused together via heatsealing, as indicated at 53 in FIG. 5. In either case, the sealed jointformed at the flanges 48, 50, 52 and 54 satisfies the gas barriercriteria sufficient to maintain the purity of the contents (i.e., gas)in the container 10 and syringe 12, if a syringe is placed in thecontainer 10.

[0022] Although the bottom portion 32 of the container is shown asrectangular in shape and having a rectangular recess or trough, avariety of shapes can be used. For example, the bottom portion 32 of thecontainer can be formed into a more complicated shape than a rectangleto approximately conform to the shape of its contents (e.g., a syringe12). In addition, the top portion 44 need not be planar. For example, asshown in FIGS. 4 and 5, the top portion 44 and the bottom portion 32 ofthe container 10 can both be nonplanar and configured to form the cavity46 when adhered together. Further, the top portion 44 and the bottomportion 32 of the container 10 can be configured to have a curvilinearcross-section (FIG. 4) with tapered ends 58 and 60, and 62 and 64,respectively (FIG. 5). The ends are adhered together along the flanges48, 50, 52 and 54 of the bottom portion and corresponding flanges 66,68, 70 and 72 of the top portion 44 of the container 10. Alternatively,the top portion 44 and bottom portion 32 of the container 10 can beformed as a unitary and integral piece of high gas barrier materialdesignated as 74 in FIG. 6 which is folded on one side 76 thereof. Thetwo, free ends 78 and 82 are then sealed with an adhesive layer 83 or byheat sealing depending on the material used to form the container 10.The container 10 and the syringe 12 are preferably clean and sterileaccording to conventional standards for surgical equipment.

[0023] In accordance with an embodiment of the invention, the container10 is preferably made of a high gas barrier material such as ametallized polymer laminate which can be sealed to retain a selected gasinside the container. The container 10 is preferably made from amaterial that is substantially impermeable to oxygen and otheratmospheric gases and substantially impermeable to sterilizing gasessuch as ethylene oxide. The syringe 12 is filled in a conventionalmanner with a unit dose of the selected gas (e.g., sulfur hexafluorideor nitric oxide). The syringe 12 is then placed within the bottomportion 32 of the container 10 with the plunger 24 at least partiallywithdrawn from the cavity 22. The container 10 is then filled withpreferably the same gas as the syringe 12 and sealed using the topportion 44 (e.g., by applying an adhesive or heat sealing along theflanges 48, 50, 52 and 54 of the bottom portion 32 to adhere to theedges of the top portion 44).

[0024] Alternatively, the container 10 can be made from a sheet 74 ofhigh gas barrier material that is folded. A gas-filled syringe can beplaced between the two free ends 78 and 82 of the sheet 74. The spacebetween the free ends is then filled with the same gas and sealed toenclose the gas and gas-filled syringe. Thus, the sealed container 10provides a sufficient gas barrier to prevent the gaseous content of thecontainer, and therefore the syringe, from leaking or diffusing outsidethe container, and to prevent atmospheric gaseous contaminants fromdiffusing into the container and the syringe. Further, the use of thesame gas inside the container as well as inside the syringe facilitatesthe maintenance of the selected gas within the syringe since any gasexchange occurring through the walls of the syringe does not dilute theunit gas dose therein. The gas within the container is generallymaintained at a pressure to inhibit diffusion of oxygen and otheratmospheric gases into the container, thereby inhibiting dilution of thegas. In embodiments, the gas in the container is at a pressure greaterthan atmospheric pressure.

[0025] In preferred embodiments, the gas is a pharmaceuticallyacceptable gas as known in the medical field which is substantially inthe absence of oxygen, air and other atmospheric gas contaminants.Examples of suitable gases include nitric oxide, nitric oxide releasingcompounds, carbon dioxide, perfluoropropane, perfluorobutane,perfluoroethane, helium and sulfur hexafluoride. Generally, the gas hasa purity level of at least 70% by volume and preferably at least about93% to about 98% by volume. In embodiments, the gas is at least about97% pure. In preferred embodiments, the syringe and the container arefilled with the same gas having substantially the same purity to inhibitdiffusion of gases between the gas in the cavity of the container andcavity of the syringe barrel.

[0026] As stated previously, the high gas barrier material for thecontainer 10 prevents diffusion of gas molecules from the atmospherethrough the container walls and therefore dilution or contamination ofthe unit gas dose within the syringe 12. The shelf life of the unit gasdose is determined by the rate at which gaseous contaminants such asoxygen molecules from the surrounding atmosphere diffuse into thecontainer 10, or the rate at which the selected gas inside the container10 diffuses out. The following formula can be used to calculate themaximum allowable gas transmission rate GTR_(MAX) for the containermaterial:${GTR}_{MAX} = {V \times \frac{\left( {1 - P} \right)}{A \times S}}$

[0027] where V is the volume of the container 10, P is the minimumacceptable purity of the unit gas dose in the syringe 12, A is thesurface area of the container 10, and S is the desired shelf life of theunit gas dose in the syringe 12.

[0028] By way of an example, a unit dose of sulfur hexafluoride of atleast ninety-five percent (i.e., P=95%) purity is desired. The syringe12 is packaged in a container 10 having a volume V of 20 cubic inchesand a surface area A of 64 square inches. A one year shelf life isdesired. The maximum allowable gas transmission rate GTR_(MAX) for thecontainer 10 material is therefore 0.0156 cubic inches per square inchesper year (or 0.07 cc per 100 square inches per 24 hours). A purity levelof 95% in the example above was chosen for illustrative purposes only.The minimum acceptable purity level of gas can vary, depending on thetype of gas used and the application for its use. Embodiments providinghigher or lower priority levels are covered under the scope of thepresent invention.

[0029] Suitable materials for the container 10 can include, but are notlimited to, metal foils such as aluminized foil laminates. Otherexamples of container 10 material include laminates having one or moremetallized layers of nylon, oriented polypropylene (OPP), polyethylene(PE), ethylene vinyl alcohol (EVOH), polyethylene terephthalate (PET),low density polyethylene (LDPE), medium density polyethylene (MDPE),and/or cellophane. A lacquer coating can also be used to create a coldseal.

[0030] The container can be made from a suitable gas impermeablelaminate having a sufficiently low permeability to inhibit orsubstantially prevent the diffusion of air or oxygen from the atmosphereinto the container and to inhibit diffusion of the medical gas in thesyringe and container from diffusing outward. The container formed fromgas impermeable films are also impermeable to ethylene oxide so thatother forms of sterilization must be used. Gamma radiation atconventional sterilizing dosages can be used to effectively sterilizethe syringe and contents.

[0031] Suitable laminated films include materials sold under thetrademark ACLAR by Ted Pella, Inc. which is a transparentfluorinated-chlorinated thermoplastic. Other materials include silicacoated polyester films sold under the tradename Clearfoil by RollprintPackaging Products, Inc. of Addison, Illinois, a polypropylene,polyethylene, polyethylene vinyl alcohol and Bynel laminate sold underthe trademark EVALIGHT by DuPont. Preferably, the container 10 issufficiently impermeable to oxygen and other atmospheric gases toprovide a shelf life of the syringe of about one year where the gaspurity in the syringe is substantially unchanged. In furtherembodiments, the packaged syringe has a shelf life of at least about 6months to about 5 years, and typically about 1-2 years.

[0032] Some of the gases used in surgery have large molecules whichcannot pass through polymeric or metallic films as readily as oxygen.Oxygen and other gaseous contaminants cannot dilute the unit gas dose inthe syringe 12 unless one of two conditions exists. First, if thecontainer 10 material allows some of the selected gas in the containerto diffuse out into the atmosphere, then the volume of gas lost in thecontainer 10 is replaced with other gas constituents from theatmosphere. Second, if the pressure in the container 10 is less thanatmospheric pressure outside the container, then the gaseouscontaminants may diffuse into the container regardless of whether anyinterior container gas diffuses out. If the pressure in the container 10is essentially maintained above the atmospheric pressure, then thecontainer material can be chosen on the basis of the transmission rateof the gas in the container. In cases where the selected gas ischaracterized by large molecules, materials providing considerably lowergas barriers can be used as compared with materials providing barriersto gases with relatively small molecules. If the pressure in thecontainer is not maintained above atmospheric pressure, then the highestrelevant gas transmission rate, which is typically the gas transmissionrate of oxygen in the surrounding atmosphere, is preferably used as thebasis for selecting a container material.

[0033] A controlled atmosphere of a selected gas inside the container 10can be achieved in a number of ways. For example, a form/fill/sealmachine can be used. The form/fill/seal machine provides an evacuatedassembly area therein which is filled with the selected gas. The web(s)of a high gas barrier material selected to construct one or morecontainers 10 is feed into the area. One part of the container can beformed, for example, with a recess or trough of sufficient size toaccommodate a pre-filled gas syringe therein. The container constructionis then completed by enclosing the syringe within the container using,for example, another piece of the web to cover the recess. The otherpiece of the web can be sealed against the first part of the web usingan adhesive or heat sealing. The controlled gaseous assembly area,therefore, ensures that the container is filled with the same gas as thesyringe to avoid the aforementioned problem of dilution caused by gascontaminants mixing with the contents of the syringe inside thecontainer 10.

[0034] Alternatively, a controlled atmosphere of a selected gas insidethe container 10 can be achieved by providing the container with a valvewhich permits evacuation of a sealed container having a pre-filled gassyringe enclosed therein and subsequent filling of the container withthe selected gas. Further, the container 10 need not be provided with asyringe 12 at all. In accordance with an embodiment of the presentinvention, the container 10 can be filled with a selected gas (e.g.,using a form/fill/seal machine that does not insert a syringe prior tosealing, or by evacuation, ejection with a selected gas and sealing).The container 10 containing the selected gas can then be drawn into anempty syringe by puncturing the container 10 with a needle and drawingthe gas into the syringe cavity 22 with the plunger 24. Alternatively, asyringe can be constructed with a sufficiently gas impermeable tubularhousing 14, stopper 28 and cap 30 combination to obviate the need for acontainer 10. The syringe can therefore be pre-filled with a selectedgas prior to use and prevent contamination of the gas therein until thecap 30 is removed.

[0035] In a further embodiment shown in FIG. 7, a pressurized gascanister 100 is coupled to a syringe 102 for filling the syringe 102with a medical gas. The canister can be made of metal, plastic, glass orother suitable materials capable of maintaining the gas under sufficientpressure to fill the syringe. The canister 100 includes a manuallyoperated valve 104 having an actuating button 105. The valve 104 has acoupling member 106, such as a threaded coupling, for connecting to afilter housing 108. The filter housing 108 is typically a HEPA filter asknown in the art to remove particulates and other impurities. An outletcoupling 110 is provided in the filter housing 108 for connecting to thesyringe 102. The syringe 102 in the embodiment illustrated has a luerlock type fitting for coupling to the filter. In further embodiments,the syringe can have a needle for piercing a septum or membrane on theoutlet coupling 110 of the filter housing 108. Alternatively, thesyringe can have a tapered tip for attaching to the coupling 110 and forreceiving a needle or other delivery outlet or device. In use, thebutton 105 is depressed to release the gas from the canister to fill thesyringe. Typically, the canister containers a sufficient amount of gasto flush the syringe to remove any contaminants which may be present. Inembodiments of the invention, the syringe and canister are enclosed in acontainer 112 having a cavity 114 containing the same gas as the gas inthe canister. Preferably, the gas in the canister and the container 112is substantially pure in the absence of oxygen and other atmosphericgases. The container 112 is made from the same materials as in theprevious embodiments.

[0036] The container 10, whether it is provided with a syringe 12therein or not, is preferably sterilized so it can be used in surgery,for example. A number of methods for sterilization can be used. Thecontainer 10 can be sterilized, for example, as it is being formedinside a form/fill/seal machine. The syringe can be sterilized before itis inserted into a sterile chamber in the form/fill/seal machine, or thesyringe 12 and new formed container 10 can both be sterilized as theyare assembled together. A container 10 containing only gas and nosyringe can be sterilized inside a form/fill/seal machine or besterilized after it is assembled and before it is filled with gas if anatmosphere-controlled assembly and fill area is not available.

[0037] In accordance with the present invention, a pre-filled packagecontaining a unit dose of medical gas and method of making same isprovided. The pre-filled package can be a package, a package containinga syringe or a syringe having a gas impermeable chamber. The pre-filledpackage prevents contamination of the gas therein for use in a number ofapplications, such as injection of a gas bubble into a patient's eye fortreating a retinal tear, or injection of carbon dioxide into a bloodvessel to displace blood and allow an improved field of view duringpercutaneous angioscopy. The material with which the package is made isselected to maintain a desired purity level of gas within the package.Further, the aforementioned problems associated with dispensingexpensive gases from a tank in preparation for a medical procedure areavoided.

[0038] In the method of the invention, the syringe is removed from thecontainer and the delivery device, such as a needle, is introduced inthe desired location in the body of the patient being treated. Thesyringe plunger is then depressed to inject a unit dose of the gas intothe patient. The gas can be injected into a vein or vessel, the ocularcavity of an eye during eye surgery, the spinal column, and the like, asknown in the medical and surgical field. When performing surgery in theeye, such as retinal surgery, the injected gas is an ophthalmologicallyacceptable gas.

[0039] While certain advantageous embodiments have been chosen toilluminate the invention, it will be understood by those skilled in theart that various changes and modifications can be made herein withoutdeparting from the scope of the invention as defined in the appendedclaims.

What is claimed is:
 1. A gas syringe for injecting a gas into the bodyof an animal, said syringe comprising: a prefilled gas syringecontaining a unit dose of a pharmaceutically acceptable gas, said gasbeing substantially in the absence of air, said syringe including asyringe barrel with a gas delivery outlet, and a plunger slidablyreceived in said syringe barrel for expelling said unit dose of said gasthrough said delivery outlet; and a container enclosing said gas syringeto prevent contact of said gas syringe with air and contaminantsexternal to said container, said container having an internal volumecontaining said gas substantially in the absence of air, said containerbeing made of a substantially gas impermeable material and saidcontainer having an internal pressure to inhibit diffusion of air andcontaminants into said container.
 2. The gas syringe of claim 1, whereinsaid container has an internal surface area defining said unit dose ofsaid gas, and said gas in said syringe has a purity of at least about95%, said gas having a shelf life of at least one year, said gas barriermaterial to have a maximum allowable gas transmission rate determinedusing V×(1−p)/(A×S), wherein V is a volume of said container, p is thepurity of said gas, A is the internal surface area of said container,and S is said shelf life.
 3. The gas syringe of claim 1, wherein saidgas is selected from the group consisting of nitric oxide, nitricoxide-releasing compounds, carbon dioxide, perfluoropropane,perfluorobutane, perfluoroethane, helium, and sulfur hexafluoride. 4.The gas syringe of claim 1, wherein said gas barrier material isselected from the group consisting of a metal foil, an aluminized foillaminate, and a laminate having at least one metallized layer of atleast one layer of nylon, polypropylene, ethylene vinyl alcohol,polyethylene terephthalate, low density polyethylene, medium densitypolyethylene or cellophane.
 5. The syringe of claim 1, wherein said gasdelivery outlet is a needle.
 6. The syringe of claim 1, wherein said gasis substantially free of oxygen and is at least about 93% by volumepure.
 7. The syringe of claim 1, wherein said gas in said container isat a pressure above atmospheric pressure.
 8. The syringe of claim 1,wherein said container is made from a metal foil laminate.
 9. Thesyringe of claim 1, further comprising a canister containing saidpressurized gas, said canister having an outlet removably coupled tosaid delivery outlet for supplying said gas to said syringe.
 10. Amethod of introducing a gas into the body of an animal comprising thesteps of: providing a clean and sterile packaged, prefilled syringehaving a syringe barrel, delivery outlet and plunger, said syringecontaining a unit dose of a pharmaceutically acceptable gas, said gasbeing substantially free of air, wherein said prefilled syringe isenclosed in a container, said container being formed from a materialsubstantially impermeable to air and said pharmaceutically acceptablegas and having an internal volume surrounding said syringe and beingfilled with said gas at a pressure at least substantially equal toatmospheric pressure, removing said syringe from said container, andintroducing said delivery outlet into an animal and injecting said gasinto said animal.
 11. The method of claim 10, wherein said deliveryoutlet is a needle or cannula.
 12. The method of claim 10, wherein saidpharmaceutically acceptable gas has a purity of at least about 70% byvolume.
 13. The method of claim 10, wherein said pharmaceuticallyacceptable gas has a purity of about 93% to 98% by volume.
 14. Themethod of claim 10, wherein said container has a gas permeability toprovide a shelf life of said gas in said syringe of at least one year.15. The method of claim 10, wherein said pharmaceutically acceptable gasis selected from the group consisting of nitric oxide, nitricoxide-releasing compounds, carbon dioxide, perfluoropropane,perfluoroethane, perfluorobutane, helium and sulfur hexafluoride. 16.The method of claim 10, wherein said container is made from a laminatematerial having at least one metal foil layer and a layer selected fromthe group consisting of nylon, polypropylene, polyethylene, ethylenevinyl alcohol, polyethylene terephthalate and cellophane.
 17. The methodof claim 10, wherein said container is formed from a material having asufficiently low gas permeability whereby the purity of said gas in saidcontainer is substantially unchanged after about one year.
 18. Themethod of claim 10, wherein said container is made from a substantiallyoxygen impermeable-material.
 19. The method of claim 10, wherein saidgas in said container is at a pressure above atmospheric.
 20. A methodof introducing a gas into the eye during eye surgery, said methodcomprising the steps of providing a clean and sterile prefilled syringecontaining a unit dose of a pharmaceutically acceptable gas and beingsubstantially free of air and oxygen, said syringe having a syringebarrel, a gas delivery outlet, and a plunger, said syringe beingcompletely enclosed in a substantially gas impermeable container, saidcontainer having an internal volume surrounding said syringe and beingfilled with said pharmaceutically acceptable gas at a pressure at leastsubstantially equal to atmospheric pressure, removing said syringe fromsaid container, and introducing said gas delivery outlet of said syringeinto the eye of a patient and introducing said gas into the eye.
 21. Themethod of claim 20, wherein said pharmaceutically acceptable gas has apurity of at least about 93% k to 98% by volume. .
 22. The method ofclaim 20, wherein said pharmaceutically acceptable gas is selected fromthe group consisting of nitric oxide, nitric oxide-releasing compounds,carbon dioxide, perfluoropropane, perfluoroethane, perfluorobutane,helium and sulfur hexafluoride.